The Activity-Regulated Cytoskeletal-Associated Protein (Arc/Arg3.1) Is Required for Memory Consolidation of Pavlovian Fear Conditioning in the Lateral Amygdala
Open Access
- 19 November 2008
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 28 (47), 12383-12395
- https://doi.org/10.1523/jneurosci.1662-08.2008
Abstract
The activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is an immediate early gene that has been widely implicated in hippocampal-dependent learning and memory and is believed to play an integral role in synapse-specific plasticity. Here, we examined the role of Arc/Arg3.1 in amygdala-dependent Pavlovian fear conditioning. We first examined the regulation of Arc/Arg3.1 mRNA and protein after fear conditioning and LTP-inducing stimulation of thalamic inputs to the lateral amygdala (LA). Quantitative real-time PCR,in situhybridization, Western blotting and immunohistochemistry revealed a significant upregulation of Arc/Arg3.1 mRNA and protein in the LA relative to controls. In behavioral experiments, intra-LA infusion of an Arc/Arg3.1 antisense oligodeoxynucleotide (ODN) was observed to be anatomically restricted to the LA, taken up by LA cells, and to promote significant knockdown of Arc/Arg3.1 protein. Rats given intra-LA infusions of multiple doses of the Arc/Arg3.1 ODN showed an impairment of LTM (tested ∼24 later), but no deficit in STM (tested 3 h later) relative to controls infused with scrambled ODN. Finally, to determine whether upregulation of Arc/Arg3.1 occurs downstream of ERK/MAPK activation, we examined Arc/Arg3.1 expression in rats given intra-LA infusion of the MEK inhibitor U0126. Relative to vehicle controls, infusion of U0126 impaired training-induced increases in Arc/Arg3.1 expression. These findings suggest that Arc/Arg3.1 expression in the amygdala is required for fear memory consolidation, and further suggest that Arc/Arg3.1 regulation in the LA is downstream of the ERK/MAPK signaling pathway.Keywords
This publication has 81 references indexed in Scilit:
- Phosphorylation of ERK/MAP kinase is required for long-term potentiation in anatomically restricted regions of the lateral amygdala in vivoLearning & Memory, 2008
- Temporal requirement of C/EBPβ in the amygdala following reactivation but not acquisition of inhibitory avoidanceLearning & Memory, 2007
- Increased Expression of the Immediate-Early Gene Arc/Arg3.1 Reduces AMPA Receptor-Mediated Synaptic TransmissionNeuron, 2006
- Arc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA ReceptorsNeuron, 2006
- Arc/Arg3.1 Interacts with the Endocytic Machinery to Regulate AMPA Receptor TraffickingNeuron, 2006
- Electroconvulsive seizure‐induced gene expression profile of the hippocampus dentate gyrus granule cell layerJournal of Neurochemistry, 2006
- Lesions of the Basal Amygdala Block Expression of Conditioned Fear But Not ExtinctionJournal of Neuroscience, 2005
- Postsynaptic Receptor Trafficking Underlying a Form of Associative LearningScience, 2005
- An egr-1 (zif268) Antisense Oligodeoxynucleotide Infused Into the Amygdala Disrupts Fear ConditioningLearning & Memory, 2004
- NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdalaEuropean Journal of Neuroscience, 2004